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Lymphangioleiomyomatosis Medication

  • Author: Joel Moss, MD, PhD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: Jul 27, 2015
 

Medication Summary

The goals of pharmacotherapy for lymphangioleiomyomatosis (LAM) are to reduce morbidity and to prevent complications. However, new experimental drug therapies, such as the following, target the underlying disease.

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Immunosuppressant agents

Class Summary

Immunosuppressants may inhibit T-lymphocyte activation and proliferation that come about from antigenic and cytokine stimulation.

Sirolimus (Rapamune)

 

LAM involves lung tissue infiltration with smooth muscle-like cells that harbor inactivating mutations of the tuberous sclerosis complex (TSC) gene (LAM cells). Loss of TSC gene function activates the (mechanistic target of rapamycin (mTOR) signaling pathway, resulting in cellular proliferation and release of lymphangiogenic growth factors. Sirolimus inhibits the activated mTOR pathway and thus the proliferation of LAM cells. It received FDA approval for treatment of LAM in May 2015. 

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Antimalarials, Aminoquinoline

Class Summary

Aminoquinolines may inhibit prostaglandin effects.

Chloroquine Phosphate (Aralen)

 

Chloroquine is an autophagy inhibitor that appears to induce the death of TSC2-deficient cells when given in combination with sirolimus and is being tested in an ongoing clinical trial.

Anti-inflammatory activity results from lymphocyte transformation suppression. It inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Chloroquine may also have photoprotective effect.

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Antineoplastics, Aromatase Inhibitor

Class Summary

Aromatase inhibitors can cause a significant reduction in plasma estrogen.

Letrozole (Femara)

 

Letrozole is an aromatase inhibitor with antiestrogenic effects that is being tested in LAM.

It is a nonsteroidal competitive inhibitor of the aromatase enzyme system. It inhibits the conversion of androgens to estrogens. Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis.

Patients treated with letrozole do not require glucocorticoid or mineralocorticoid replacement therapy.

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Contributor Information and Disclosures
Author

Joel Moss, MD, PhD Deputy Chief, Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health

Joel Moss, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American Society for Clinical Investigation, American Society for Biochemistry and Molecular Biology, American Thoracic Society, Association of American Physicians, Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Arnold S Kristof, MDCM, FRCPC Associate Professor of Medicine, Department of Medicine, Respiratory and Critical Care Divisions; Associate Member, Department of Microbiology and Immunology; Research Director, Meakins-Christie Laboratories, McGill University Faculty of Medicine; Attending Physician, Respiratory and Critical Care Divisions, McGill University Health Centre, Royal Victoria Hospital, Canada

Arnold S Kristof, MDCM, FRCPC is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Royal College of Physicians and Surgeons of Canada, American Society for Biochemistry and Molecular Biology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

John A Kelly, MB, BCh, MD † Assistant Professor of Medicine and Microbiology and Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center.

Acknowledgments

This work was supported in part by the Division of Intramural Research, National Institutes of Health, National Heart, Lung, and Blood Institute (J.M.) as well as National Institutes of Health R01-CA125436, Tuberous Sclerosis Alliance, LAM Foundation, LAM Canada (A.K.).

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